SETX Antibodies

Structure of SETX

The senataxin protein encoded by the SETX gene is a large multifunctional protein with a molecular weight of approximately 303 kDa. This protein belongs to the Upf1-like helicase superfamily, and its precise molecular weight may vary depending on the transcript subtype or species. The following table lists the molecular weight and main functional domain characteristics of SETX proteins in different species:

The core structure of the Senataxin protein is a multi-domain complex. Its N-terminal contains a helicase domain composed of seven conserved motifs, which is responsible for binding ATP and catalyzing the dissociation of RNA/DNA double strands. The C-terminal region is crucial for its interaction with various proteins, such as RNA polymerase II, and for recruiting DNA repair factors. This protein plays a core role in gene transcription termination, R-loop resolution and maintaining genomic stability through its unique biochemical activity.

Fig. 1 SETX (p.Thr2373Ile) mutation is predicted to alter senataxin's 3D structure.¹

Key structural properties of SETX:

• Contains the conserved SF1 superfamily helicase domain
• Characteristic nucleic acid binding channels
• C terminal contains important protein interaction area

Functions of SETX

The core function of the senataxin protein encoded by the SETX gene is to maintain genomic stability, especially playing a key role in transcription and DNA damage repair processes. However, it is also widely involved in various biological processes such as the development and functional maintenance of the nervous system.

Unlike many structurally specialized DNA repair enzymes, senataxin, as a multifunctional nuclease, achieves real-time monitoring and repair of genomic risks during transcription through its physical and functional coupling with transcription machines, which explains why its functional mutations specifically cause neurodegenerative diseases.

Applications of SETX and SETX Antibody in Literature

1. Ramachandran, Shaliny, et al. "Hypoxia-induced SETX links replication stress with the unfolded protein response." Nature communications 12.1 (2021): 3686. https://doi.org/10.1038/s41467-021-24066-z

The article indicates that tumor hypoxia can induce the expression of SETX, an RNA/DNA helicase that can clear R-loop, reduce DNA damage and maintain replication rate. Its regulation depends on the PERK/ATF4 unfolded protein response pathway, thereby connecting the stress response with the DNA damage repair mechanism.

2. Said, Maha, et al. "FANCD2 promotes mitotic rescue from transcription-mediated replication stress in SETX-deficient cancer cells." Communications Biology 5.1 (2022): 1395. https://doi.org/10.1038/s42003-022-04360-2

The article indicates that the deletion of SETX leads to transcription-replication conflicts and the accumulation of R-loops, triggering replication stress and chromosomal instability. Fanconi anemia pathway protein FANCD2 repairs this damage by promoting XPF/ MUS81-dependent DNA synthesis. Co-deletion of SETX and FA genes can specifically inhibit cancer cell proliferation and has the potential for synthetic lethal treatment.

3. Rao, Satyajeet, et al. "Senataxin RNA/DNA helicase promotes replication restart at co-transcriptional R-loops to prevent MUS81-dependent fork degradation." Nucleic Acids Research 52.17 (2024): 10355-10369. https://doi.org/10.1093/nar/gkae673

The article indicates that SETX promotes replication fork reactivation by unwinding the R-loop, and it works in synergy with the MUS81-LIG4-ELL pathway to alleviate transcription-replication conflicts. The absence of SETX leads to DNA2-mediated replication fork degradation and, together with DDX17, inhibits R-loop-mediated replication stress.

4. Nanetti, Lorenzo, et al. "SETX mutations are a frequent genetic cause of juvenile and adult onset cerebellar ataxia with neuropathy and elevated serum alpha-fetoprotein." Orphanet journal of rare diseases 8.1 (2013): 123. https://doi.org/10.1186/1750-1172-8-123

This study conducted genetic analysis on 22 Italian patients with ataxia accompanied by eye movement disorders and found that 57% carried SETX mutations (AOA2 type), and 14 novel mutations and 3 known mutations were identified. The patients mainly presented with gait ataxia, facial movement disorders and elevated AFP, but none of them had significant apraxia of eye movement, suggesting that SETX is the main pathogenic gene for this phenotype.

5. Szaluś-Jordanow, Olga, et al. "A primary multiple pleomorphic rhabdomyosarcoma of the heart in an adult dog." BMC Veterinary Research 19.1 (2023): 137. https://doi.org/10.1186/s40478-021-01277-5

The article indicates that the p.ter8met de novo mutation in the SETX gene leads to early-onset severe peripheral neuropathy. Transcriptional network analysis shows that it is highly associated with ALS4 (functional acquisition) rather than AOA2 (functional loss) characteristics, confirming that this mutation is pathogenic and expanding the phenotypic spectrum of SETX-related diseases.

Creative Biolabs: SETX Antibodies for Research

Creative Biolabs specializes in the production of high-quality SETX antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom Myoglobin Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our SETX antibodies, custom preparations, or technical support, contact us at email.